Was gluten intake restricted in advance of biopsy (may be inadvertent if a household member is following a gluten-free diet)?

No

Yes

### No
Review biopsies with an experienced pathologist. Assess for collection of a minimum of 4 distal duodenal biopsies and 1-2 biopsies of duodenal bulb (preferably from 9 or 12 o’clock position). Consider repeating serological assays at a different laboratory as variability may exist. If symptomatic, ensure that alternative explanations for the patient’s symptoms have been excluded (e.g., IBD, other autoimmune disease, Helicobacter pylori, IBS). Consider wireless capsule endoscopy to exclude gross evidence of distal villous atrophy as a small subset of patients may lack duodenal mucosal injury if there are other concerning signs, such as growth failure. Send HLA DQ2 (DQA1\*05:01/05:05 and DQB1\*02:01/02:02)/DQ8 (DQA1\*03:01 and DQB1\*03:02), genotyping to rule in or out the possibility of celiac disease.

### Positive
Patient may have potential (or latent) celiac disease (provided sufficient gluten intake preceding biopsy, sufficient and well-oriented biopsy sampling, consistent results on repeat serologic assays, lack of evidence for IBD). Continue to follow on an unrestricted, gluten-containing diet.^[1](#fhir-question-154e033da684832eef8780b02200886f),[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1)^ Consider treatment for celiac disease if laboratory evidence remains strong and compelling clinical circumstances warrant immediate undertaking of a strict gluten-free diet (e.g., significant symptoms, advancing pubertal state with growth deficits).^[1](#fhir-question-154e033da684832eef8780b02200886f)^ Consider repeat biopsy if elevated TTG-IgA is persistent over time (at least 3-6 months apart), or if clinical suspicion increases (such as poor growth or other severe symptoms).
If the patient has a Marsh I/II lesion, this may still be consistent with celiac disease, though care should be taken in such cases prior to rendering the diagnosis. Under these circumstances, if HLA typing is positive for DQ2 (DQA1\*05:01/05:05 and DQB1\*02:01/02:02) and/or DQ8 (DQA1\*03:01 and DQB1\*03:02), and the patient has had sufficient gluten intake, reliable serology, well-oriented biopsies confirmed by pathologist, and lack of other explanation for the mucosal findings (i.e., no Helicobacter pylori infection and no chronic use of NSAIDs), a Marsh I or II lesion along with this clinical and serological data supports a celiac disease diagnosis. Consider treatment with a gluten-free diet under these circumstances. Monitor for decline of the patient’s serologies and symptoms. Consider a repeat biopsy following treatment to evaluate for mucosal recovery. If there are questions raised regarding the clinical, histologic, or laboratory evidence and the patient is not in a vulnerable state, consider observation with repeat serologic and histologic assessment.

### Yes
If celiac disease is suspected clinically, consider gluten challenge (roughly 2 servings of gluten - e.g., 2 slices of wheat-based bread - daily for 6-8 weeks)^[3](#fhir-question-9231a113a2544f625c3e0970bc3af532),[4](#fhir-question-2bbe3f3e2bd385e5b274173883f2d6fb)^ with subsequent reassessment of serologies and possible repeat biopsy. Consider alternative explanations of the patient’s symptoms and positive serologies. If the family declines to liberalize gluten, follow the patient symptomatically as well as serologically to be sure there is improvement of both. Gluten challenge should be reconsidered at a later date in such circumstances.

Serology is negative though biopsy reveals a Marsh lesion that may be consistent with celiac disease.

If TTG-IgA and EMA IgA were negative, was IgA sufficiency confirmed OR was IgG based testing (DGP IgG OR TTG IgG) also sent and confirmed negative?

### Positive
Most likely not celiac disease. Seronegative celiac disease is very rare in children. If strong clinical suspicion persists, options include: repeat endoscopy with biopsy while remaining on gluten-containing diet; assess more distal small bowel and colon for Crohn’s disease or evidence of celiac disease. If suggestive of celiac disease, consider trial of a gluten-free diet. If lesions remain unchanged following initiation of a strict gluten-free diet, continue to reassess for alternative causes of villous atrophy. If symptomatic response to a gluten-free diet, follow symptoms and serology and consider confirming recovery with endoscopy and biopsy after 12 months on a gluten-free diet. Consider re-challenge with gluten (roughly 2 servings of gluten - e.g., 2 slices of wheat-based bread - daily for 6-8 weeks)^[3](#fhir-question-9231a113a2544f625c3e0970bc3af532),[4](#fhir-question-2bbe3f3e2bd385e5b274173883f2d6fb)^ after histologic resolution to confirm recurrence.

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